The prevalence of urolithiasis, or kidney stone disease, is increasing with an aging population. A recent German epidemiology study showed an increase in the prevalence of kidney stones in the general German population from about 0.5% in 1971 to about 1.5% in 2000. (Hesse A. et al. European Urology 2003, 44, 709-713). Urolithiasis is also a significant health problem in the United States. It is estimated that between 5-10% of the general population will develop a urinary concretion during their lifetime. (Pak, C. T. Diseases of the Kidney, 5th Edition; Boston; Little, Brown & Co.; 1993; pp. 729-743). The peak onset of urolithiasis is typically between 20 and 30 years of age, and males are effected more often then females.
Since being introduced in the 1980s, minimally invasive procedures such as lithotripsy, as well as ureteroscopy, have become the preferred methods for treatment in a majority of cases of concretions in the ureter, and have a potential for application to concretions that develop in other parts of the body such as the pancreas and the gallbladder. Lithotripsy is a medical procedure that uses energy in various forms such as acoustic shock waves, pneumatic pulsation, electrical hydraulic shock waves, or laser beams to break up biological concretions such as urinary calculi (e.g., kidney stones). The force of the energy, when applied either extracorporeally or intracorporeally, usually in focused and continuous or successive bursts, comminutes a kidney stone into smaller fragments that may be extracted from the body or allowed to pass through urination. Applications to other concretions formed in the body, such as pancreatic, salivary and biliary stones as well as the vascular system, are currently underway in several research laboratories across the United States and Europe.
As mentioned above, the introduction of extracorporeal shockwave lithotripsy (ESWL) in 1980 changed the management of renal and ureteral calculous disease from a surgical to a noninvasive procedure. ESWL is a procedure in which renal and ureteral calculi are broken up into smaller fragments by shock waves. These small fragments then can pass spontaneously. All shock wave generators are based on the geometrical principle of an ellipse. Shock waves are created at the first focal point of an ellipsoid (‘F1’), within the half ellipse, and are directed towards the second focal point (‘F2’), within the patient. The focal zone is the area at F2 where the shock wave is concentrated. The focal zone of the original Dornier HM3 exceeded 2 cm; most new electromagnetic generators have focal zones that average only 6 mm. The energy in these shock waves breaks a larger stone into smaller stones. This noninvasive approach allows patients to be rendered stone-free without surgical intervention or endoscopic procedures.
However there are several complications which can result from standard ESWL. Clinical experience demonstrates that a typical fragmentation rate of about 85%, and a stone-free rate of about 65-70%, is achievable with ESWL. A major problem with the procedure is that when kidney stones are fragmented the energy is sufficient to widely distribute them throughout the ureter and kidney. Further, fragments might become undetectable (e.g., too small to be imaged by fluoroscopy) but still too big to be easily passed. In addition, after the stones fragment, the shock wave treatment still focuses on the focal point F2, and the redistribution of the stones could move them outside the range of the treatment. Therefore, during the procedure it would be highly beneficial to confine the kidney stone and the resulting fragments into a narrow space within the focal point of F2. An improvement in this approach, which is described herein, would be to place a plug behind and in front of the stone, thereby confining the stone to a particular space. After the procedure the plugs could be removed and the smaller stones allowed to pass.
A different approach to the treatment of kidney stones is intracorporeal lithotripsy. A common approach employs laser energy at 2100 nm, generated by a holmium:YAG laser. A coumarin dye laser may also be used. The laser produces a vaporization bubble at the tip of the fiber optic and the energy is transferred to the stone and leads to fragmentation. However, proximal ureteral stone migration during laser lithotripsy accounts for a high percentage of ureteroscopic failures. In addition there is an electro-hydraulic technique, which utilizes electric discharge, ignited between two electrodes disposed within the probe and producing shock wave, expanding towards the concretion through liquid phase, which surrounds the concretion. Various mechanical anti-migration backstops have been developed and involve the placement of these devices behind the kidney stone, with respect to the laser or shock wave, and subsequent extraction of the smaller stones post fragmentation. A simpler approach, described herein, would be to introduce a temporary plug behind the stone, preventing the stone and its fragments from migrating further up the urethra or kidney. This approach would require a plug that was easily removable after the fragmentation.
It is an object of the invention to facilitate lithotripsy. The invention generally includes the use of a material (inverse thermosensitive polymers) that exists in liquid form and is transformed into a gel inside the body of a patient. The inverse thermosensitive polymers of the invention generally includes the use of a material that exists in liquid form at temperatures below about body temperature and as a gel at temperatures about at and above body temperature. The temperature at which the transition from liquid to gel occurs is referred to as the inverse thermosensitive polymer, and it can be a small temperature range as opposed to a specific temperature.